Environmental response pathways are of interest as models for conserved signal transduction pathways and as determinants of virulence among microbial pathogens. Our studies have focused on the mechanisms through which yeast cells sense and respond to changes in external pH. Two pathways that are required for growth of budding yeast Saccharomyces cerevisiae at alkaline pH and whose homologs are required for full virulence of the fungal pathogen Candida albicans: the Rim101p pathway and the MdsSp pathway. Our broad objective is to understand, for each pathway, the specific signal that is recognized, the mechanism of signal transduction, and the target genes and functions that contribute to pathogenicity. Our experimental methods employ mainly genetic and cell biological methods. Our specific aims are to identify the signal that governs Rim101p pathway activity, to determine the relationship of Mds3p/Pmd1p to transcriptional targets, and to determine the roles of C. albicans Rim101p and MdsSp target genes in virulence. Our work is relevant to public health in providing insight into how an infectious disease agent is able to grow in so many different body sites, and how it damages our cells to cause disease and death.